The correlation between plasma aprepitant concentration and antiemetic effect in Japanese gastric or esophageal cancer patients.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) are significant problems in cancer patients, but a correlation between plasma aprepitant concentration and antiemetic effect has not been reported. This study aimed to characterize the correlation between plasma aprepitant concentration and clinical antiemetic effect in a limited group of Japanese gastric or esophageal cancer patients. METHODS: Thirty-three Japanese cancer patients receiving cisplatin-based chemotherapy for the first time following oral aprepitant (125 mg on day 1 and 80 mg on days 2 and 3) were enrolled. The plasma aprepitant concentrations 48 h after the first administration were determined using liquid chromatography-mass spectrometry. Patients were allocated to the high-concentration group (plasma aprepitant concentration was >331.1 ng/ml) or the low-concentration group (plasma aprepitant concentration was ≤ 331.1 ng/ml) to investigate the relationship between plasma aprepitant concentration and antiemetic effects. RESULTS: No significant differences were found between the two groups in terms of percentage of CINV prevention. Of 13 patients who experienced CINV [MASCC Antiemesis Tool (MAT) score >3], those in the high-concentration group showed a significant improvement in CINV following aprepitant administration (days 1-3). CONCLUSION: The present study suggests that the antiemetic effect of aprepitant is associated with plasma aprepitant concentration. A plasma aprepitant concentration of 331.1 ng/ml may be a valid threshold for identifying its optimal antiemetic effects in Japanese gastric or esophageal cancer patients.

Inhibitory activities of selected Kampo formulations on human aldose reductase.

BACKGROUND: Diabetes complications include various symptoms such as diabetic neuropathy and cognitive disorders. Aldose reductase (AR) is the rate-limiting enzyme of the polyol pathway and is one of the causal factors of diabetes complications. In this study, the bioactivities of eight selected Kampo formulations that are currently in clinical use for diabetes complications were assessed using human AR (hAR) inhibitory activity as the primary parameter to explore the possibilities of novel clinical applications of these formulations in the treatment of diabetes complications. METHODS: The hAR inhibitory activities of four Kampo formulations that are clinically used for diabetic neuropathy, four Kampo formulations that are used for cognitive disorders, and a total of 21 component crude drugs were measured. Furthermore, the hAR inhibitory activity of Glycyrrhizae Radix preparata was measured to determine the effect of frying, which is one of the specific processing of Glycyrrhizae Radix. hAR inhibitory activity was determined by measuring the rate of decline in the absorbance of NAPH at 340 nm using 0.5 mM NADPH, 10 mM D,L-glyceraldehyde, and 3.6 mU/mL hAR in phosphate buffer solution (0.2 M, pH 6.2). RESULTS: All of the Kampo formulations exhibited significant hAR inhibitory activity; Chotosan exhibited particularly strong activity. Among the 21 crude drugs tested, adequate inhibitory activities were found for the following, in descending order of activity: Glycyrrhizae Radix > Paeoniae Radix > Chrysanthemi Flos > Cinnamomi Cortex > Phellodendri Cortex > Uncariae Uncis cum Ramulus > Bupleuri Radix. Glycyrrhizae Radix preparata exhibited an inhibitory activity that was nearly identical to that of Glycyrrhizae Radix. CONCLUSIONS: Despite their seemingly different treatment objectives, all of the Kampo formulations that are clinically used for diabetes complications demonstrated significant hAR inhibitory activity. This activity might underlie the characteristic multi-target effects of Kampo formulations. Although the overall effect of a Kampo formulation is certainly difficult to evaluate based on specific herbal medications or components, the approach as taken in this study might nonetheless contribute to further advancement in the development of new drugs via the review of proper usage and re-examination of the chemical compounds from a new perspective.

[Cost-effectiveness analysis comparing carboplatin and weekly paclitaxel with cisplatin and docetaxel in the treatment of advanced non-small cell lung carcinoma].

Carboplatin plus weekly paclitaxel (CBDCA/wPTX) and cisplatin plus docetaxel (CDDP/DTX) are the standard regimens used in the first-line treatment of advanced non-small cell lung carcinoma (NSCLC), with no significant difference in efficacy between the two. However, because there has been no study of the cost-effectiveness of CBDCA/wPTX versus CDDP/DTX to data, we compared these two regimens in the present study. Expected costs were calculated based on data from patients with Stage III b/IV NSCLC who were treated with either CBDCA/wPTX or CDDP/DTX in the Nippon Medical School Hospital. Efficacy (1-year survival rate) was determined by pooled analysis of studies extracted from the database. The cost-effectiveness ratio was calculated from expected costs and 1-year survival rates for both the CBDCA/wPTX and CDDP/DTX regimens. The expected costs per patient of the CBDCA/wPTX and CDDP/DTX regimens were ¥2, 847, 514 and ¥3, 513, 195, respectively, with 1-year survival rates of 38.6% and 42.5%, respectively. Thus, the cost-effectiveness ratio for the CBDCA/wPTX and CDDP/DTX regimens is ¥6, 750, 863 and ¥8, 329, 054, respectively. These findings clearly suggest that, CBDCA/wPTX is a more cost-effective regimen than CDDP/DTX.